There is a need to provide a biocompatible and implantable device containing islets of Langerhans, or the beta cells thereof, that can supply the hormone insulin for the purpose of controlling blood glucose levels in people with diabetes mellitus requiring insulin. Insufficient regulation of blood glucose levels in people with diabetes has been associated with the development of long-term health problems such as kidney disease, blindness, coronary artery disease, stroke, and gangrene resulting in amputation. Therefore, there is a need to replace conventional insulin injections with a device that can provide more precise control of blood glucose levels. An implantable bioartificial pancreas device which was evaluated in dogs by Monaco et al. was recently described in the following articles: "Successful treatment of diabetes with the biohybrid artificial pancreas in dogs" Transplantation 51, 43-51, January, 1991; "Biohybrid artificial pancreas: Long-term implantation studies in diabetic, pancreatectomized dogs" Science 252, 718-721, May 1991; "Transplantation of islet allografts and xenografts in totally pancreatectomized diabetic dogs using the hybrid artificial pancreas" Ann. Surg. 214 339-362 September, 1991. The device described in these articles was a chamber containing a coiled copolymer tubular membrane through which and within which blood flowed. The coiled copolymer tubular membrane had a nominal porosity of 80,000 daltons which permit free passage of nutrients and insulin but inhibit passage of the agents of the immune system (immunoisolation). Surrounding the outside of the coiled tubular membrane and within the chamber were placed islets of Langerhans. The islets of Langerhans are composed primarily of .alpha., .beta., .delta. and PP cells which synthesize and secrete the hormones glucagon, insulin, somatostatin, and pancreatic polypeptide respectively. These cells may interact in unknown ways to regulate the level of serum glucose. The islets are not in direct contact with the blood. Blood flow through the coiled tube was achieved by connecting the ends of the coiled tube to standard vascular grafts which were then anastomosed to blood vessels. In this type of device blood physically contacts and flows through the artificial coiled copolymer tubular membrane which comprises the device. The major limitation of this approach is the formation of blood clots. There is therefore a need for a device which can provide the islets with a non-clotting blood supply which also provides for rapid transfer of essential nutrients as well as glucose and insulin.
U.S. Pat. No. 4,699,141 (Rhode Island Hospital) discloses a neovascularization approach for transplanting cells by placing a ligated blood vessel in a sponge made of a material that is preferably an acrylic copolymer carrying collagen. This patent is similar to a concept for an "organoid" described later by two Thompson et al. articles, "Site-directed neovessel formation in vivo" Science, 1349-1352 September, 1988 and "Heparin binding growth factor 1 induces the formation of organoid neovascular structures in vivo" Proc. Nat'l Academy of Science, USA, 86, 7928-7932, 1989. In these articles blood vessel growth was promoted in vivo within a porous matrix consisting of a Gore-tex brand of polytetrafluoroethylene (PTFE) fibers containing absorbed growth factor. It was shown that the vascularized PTFE material served as a vehicle for the transplantation of hepatocytes in tats. However, the matrix was not used as a bioartificial pancreas and it provided no protection from the recipient's immune system.
U.S. Pat. No. 5,100,392 describes an implantable device for delivering drugs or other liquid solutions through incorporation of the device into the surrounding tissue. One of the features appears to be the use of a hollow tubular casing of a synthetic porous material that promotes growth of connective tissue. Inlet (and outlet) catheters are used to administer the fluid (including islets) directly to and from the vascularized connective tissues.
The alternative embodiment in this patent (5,100,392) for transplanting cells, such as islets of Langerhans, consisting of a plurality of hollow synthetic tubules arranged as a central cylindrical core within the outer casing will result in vascularization of the casing only leaving the tubules containing transplanted cells, such as the islets of Langerhans, either not vascularized or poorly vascularized. Although this poses no real problem for the delivery of drugs or other liquid solutions, in the case of transplanted cells, such as islets, placed within the lumens of the plurality of hollow tubules, this inner core region not being sufficiently vascularized will quickly result in injury and death of the transplanted cells or at best result, for the case of islets as the transplanted cells, in a poor glucose-insulin response with a minimal effect on the level of glucose control in a patient with diabetes mellitus. In the invention presented herein for a bioartificial pancreas, the device geometry is a thin cylindrical disk which results in precise control of the penetration depth of the ingrowing tissue and capillary bed resulting in the transplanted cells, such as the islets of Langerhans, being all at the same uniform distance from the vascularized region of the device. This will result in a more compact and easily implantable device with improved mass transfer characteristics between the transplanted cells and the vascularized region of the device. In the case of a patient with diabetes, the blood glucose control will therefore be normalized.